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04-11-2010 | Cardiometabolic | Article

CLOCK gene variant associated with sdLDL levels


Free abstract

MedWire News: A single nucleotide polymorphism (SNP) in the CLOCK gene may be associated with cardiometabolic disorders, Japanese researchers suggest.

They describe an association between the CLOCK (circadian locomotor output cycles protein kaput) 3111 T/C SNP and the amount of circulating small dense low-density lipoprotein (sdLDL) among Japanese community-dwelling people.

The involvement of CLOCK in circadian rhythmicity and the regulation of lipid and glucose metabolism has previously been documented, and disruption of either function can lead to cardiometabolic disorders.

For the purpose of the study, the researchers genotyped 365 Japanese men and women (aged 24-88 years) for CLOCK3111 T/C using a fluorescent allele-specific DNA primer assay system, and their sdLDL levels were measured by electrophoretic separation of serum lipoproteins.

Naoki Sakane (Kyoto Medical Center, Japan) and colleagues calculated the frequency of the CLOCK3111 T/C SNP in the community dwellers and the area of sdLDL. They then tested for relationships between sdLDL levels and the SNP genotype.

Writing in the journal BMC Medical Genetics, the team report that the frequency of the C allele was 0.14, with 75.9% of participants T/T homozygotes, 21.1% T/C heterozygotes, and 3.0% C/C homozygotes.

Carriers of the C allele (T/C or C/C) had a significantly lower level of sdLDL than non-carriers (0.8% vs 1.7% of total lipoproteins, respectively), and there was a significant negative correlation between the area of sdLDL and the CLOCK311 C allele .

These results were independent of age, gender, body mass index, and exercise habits.

The researchers say: "The most important finding is that the CLOCK3111 T/T homozygous form might increase the area of sdLDL, independently of potential confounding factors."

They suggest that the 3111 T/C SNP may affect the CLOCK mRNA level. This in turn could alter CLOCK protein levels, thereby disturbing lipid and glucose metabolism in peripheral organs, and circadian rhythm.

The team concludes: "Understanding the mechanisms underpinning the relationship between the environment, our circadian rhythms, and dyslipidemia in the development of cardiovascular disease will provide important pathways for both prevention and management of these conditions."

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Nikki Withers